Dapagliflozin reduces proteinuria and blood pressure but does not improve eGFR in CAD patientsTrial shows dapagliflozin impacts blood pressure and protein in transplant patients

BACKGROUND: Chronic allograft dysfunction (CAD) remains a leading cause of graft loss after kidney transplantation. Dapagliflozin (DAPA) has shown renal and cardiometabolic benefits in nontransplanted patients with chronic kidney disease. However, data on recipients with CAD are lacking. METHODS: Adult kidney transplant recipients (n = 208), with estimated glomerular filtration rate (eGFR) 25-45 mL/min/1.73 m 2 or 45-60 mL/min/1.73 m 2 with ≥10% annual decline, were randomized to receive DAPA 10 mg/d or placebo for 12 mo. The outcomes were differences in eGFR, in eGFR slopes, proteinuria, blood pressure, body mass index (BMI), and safety. RESULTS: There was no difference in eGFR between groups ( P  = 0.611). However, at month 12, eGFR was higher in the PLACEBO group (n = 102; 39.4 ± 0.9 vs 36.5 ± 0.9 mL/min/1.73 m 2 ( P  = 0.029). In the DAPA group (n = 106), the least square means (LSM) of eGFR slopes was -0.86 ± 0.65 mL/min/1.73 m 2 at the third month while remaining at -0.75 ± 0.65 mL/min/1.73 m 2 at 12 mo. The PLACEBO group presented an LSM slope of -0.34 ± 067 mL/min/1.73 m 2 at 3 mo and +0.51 ± 66 mL/min/1.73 m 2 at 12 mo. In a per-protocol analysis, patients in the DAPA group (n = 86) under angiotensin-converting enzyme inhibitor/ angiotensin receptor blockers (n = 23) did not present an eGFR dip, but those not under angiotensin-converting enzyme inhibitor/ angiotensin receptor blockers (n = 63) did. DAPA reduced proteinuria from 267 to 84 mg/g ( P  < 0.001), body weight by 2 kg ( P  = 0.02), BMI by 0.7 kg/m 2 ( P  = 0.023), systolic blood pressure by 7 mm Hg ( P  = 0.014), diastolic blood pressure from baseline to 9 mo (80.5 ± 1.2 vs 76.8 ± 1.2 mm Hg, P  = 0.021), and glycated hemoglobin in patients with diabetes by 0.5% ( P  = 0.04). The incidence of serious adverse events did not differ between groups. CONCLUSIONS: In kidney transplant recipients with CAD, DAPA did not improve eGFR compared with placebo, but presented reductions in proteinuria, blood pressure, BMI, and glycated hemoglobin, with acceptable safety.